Bonora, M.

Ciocca, M.

Ciurlia, E.

Fiore, M.R.

Fossati, P.

Gallio, E.

Iannalfi, A.

Krengli, M.

Mirandola, A.

Molinelli, S.

Orecchia, R.

Panizza, D.

Ronchi, S.

Russo, S.

Valvo, F.

Vischioni, V.

Vitolo, V.

Elsevier - Publisher Connector 

S728                                                                                                                                         3rd ESTRO Forum 2015 
 
techniques such as DTI to delineate tumour volume. <5% 
patients develop disease recurrence predominantly in the 
low-dose radiotherapy (<30 Gy) region. Identification and 
prediction of dosimetrically distinct patterns of treatment-
failure that can be correlated with specific molecular profiles 
may be useful to individualize and thereby, improve survival 
of glioblastoma. 
Reference:1. Stupp R, Hegi ME, Mason WP et al. Lancet 
Oncol. 2009; 10:459 
   
EP-1350   
Malignant mucosal melanoma in the upper aerodigestive 
tract treated with carbon ion RT at CNAO: preliminary 
results 
V. Vitolo1, P. Fossati1, M. Bonora1, A. Iannalfi1, M.R. Fiore1, V. 
Vischioni1, E. Ciurlia1, S. Ronchi1, S. Molinelli2, A. Mirandola2, 
E. Gallio2, S. Russo2, D. Panizza2, M. Ciocca2, M. Krengli3, F. 
Valvo1, R. Orecchia4 
1Centro Nazionale di Adroterapia Oncologica, Area Clinica, 
Pavia, Italy  
2Centro Nazionale di Adroterapia Oncologica, Fisica Medica, 
Pavia, Italy  
3Azienda Ospedariero - Universitaria Maggiore della Carità di 
Novara, Radioterapia, Novara, Italy  
4Istituto Europeo di Oncologia, Radioterapia, Milano, Italy  
 
Purpose/Objective: Analyze the toxicity of and response to 
carbon ion radiotherapy (CIRT) in patients diagnosed with 
malignant mucosal melanoma (MMM) in the upper 
aerodigestive tract of the head and neck area inoperable, 
with macroscopic residual/relapse after surgery or in patients 
that refused surgery. 
Materials and Methods: We analyzed data coming from 
patients with an MMM diagnosis in the head and neck area 
treated at CNAO from May 2013 to October 2014 with carbon 
ion radiotherapy at a total dose of 68,8 GyE in 16 fractions. 
The toxicity was evaluated in the scale CTCAE v.4.0 and the 
response to the disease with MRI every three months from 
CIRT. 
Results: We treated 8 patients (average age 72 years-old, 
range from 48 to 86) with MMM in the following areas: 
nasopharynx (1 patient), lacrimal duct (1 patient), nasal 
cavity (4 patients), mouth (1 patient), oropharynx (1 
patient). 3 patients were treated with macroscopic residual 
after surgery, 2 patients after post-surgical relapse with 
positive margins, 3 patients only with CIRT. Average GVT was 
31.47 cc (range 7.76-84.23 cc). 2 patients received systemic 
therapy pre-CIRT (1 out of 2 also post-CIRT). In the course of 
treatment, toxicity appeared acceptable (≤ G2 in 7 patients, 
G3 mucositis in 1 patient). The mean follow-up was 8 months 
(range 3-12). 3 months follow-up was available for 5 patients 
(1 patient completed CIRT one month ago, 2 patients died at 
2 and 3 months after CIRT for the progression of distant 
disease) and showed low grade acute toxicity (G0 in 4 
patients, G1 in 1 patient); at 3 months response evaluated 
with RECIST was CR in 2 patients and PR in 3 patients. 
Follow-up at the 6 months (available for 4 patients) 
confirmed low intermediate toxicity (G1 in all the patients), 
partial response (PR) in 3 patients and complete response 
(CR) in 1 patient. Follow-up at 9 months was available for 4 
patients, the highest toxicity was G2 in 1 patients, PR in 1 
patient and CR in 3 patients. Follow-up at 12 months was 
available only for 1 patient, with confirmed CR and toxicity 
G1. Progression disease took place in 2 patients, respectively 
at 0 and 1 months after CIRT (in both cases distant PD in 
absence of local PD). 
Conclusions: Recommended treatment for patients with MMM 
in the head and neck area is surgery followed by adjuvant 
radiotherapy. In the event of macroscopic residual or not 
resectable disease, preliminary results observed at CNAO 
confirm that CIRT guarantee good local control, allowing high 
dose on complex volume and in the proximity of critical 
organs with very low 
These data are preliminary; larger patient number and longer 
follow up are needed. 
  
EP-1351  
Efficacy of combination treatments of a NOTCH inhibitor 
and chemoradiotherapy in an orthotopic glioma model 
S. Yahyanejad1, P.V. Granton2, S. Van Hoof2, L. Barbeau1, J. 
Theys1, F. Verhaegen2, M. Vooijs1 
1GROW - School for Oncology and Development, Radiation 
oncology (Maastro Lab), Maastricht, The Netherlands  
2GROW - School for Oncology and Development, Maastro 
Clinic, Maastricht, The Netherlands  
 
Purpose/Objective: Glioblastoma multiforme (GBM) is the 
most common and malignant brain tumor in adults. 
Aggressive multimodal treatment using surgery followed by 
radiotherapy and chemotherapy extends the median survival 
of GBM patients to approximately one year after diagnosis. 
Treatment is not curative because of the intrinsic and 
acquired radiation resistance of a subpopulation of tumor 
cells. Notch inhibition has been shown to impair the 
tumorigenic capacity of these cells as well as enhance their 
sensitivity towards radiation. Therefore, we investigated if a 
highly potent and clinically approved Notch pathway inhibitor 
improves tumor control when combined with radiotherapy 
and chemotherapy in an orthotopic GBM mouse model.  
Materials and Methods: To investigate combinations between 
standard of care treatment and Notch inhibitors, we used a 
three dimensional spheroid assay from commercially 
available and primary glioma cell lines in which spheroid 
volume growth delay can be quantitatively monitored in 
individual spheroids. In addition, we assessed the expression 
of the putative glioma stem cell marker CD133 performing 
flow cytometry. Furthermore, therapeutic efficacy was 
evaluated in an orthotopic glioma tumor model wherein 
tumor progression was evaluated using bioluminescence (BLI) 
and contrast-enhanced micro-computed tomography (CT) 
imaging and confirmed using histopathological analysis. 
Dedicated small animal treatment planning software (SmART-
Plan) was used to create irradiation plans to deliver a 
conformal dose of 8Gy to the tumor with minimal normal 
tissue exposure. A small animal precision irradiation platform 
(PXI, XRAD 225Cx, CT, USA) was used for micro-CT imaging 
and radiation delivery. 
Results: Notch blockade alone did not affect the sphere 
volume compared to control, whereas combination treatment 
with radiation resulted in a substantial spheroid growth delay 
(p=0.004). Radiation treatment enhanced the expression of 
the stem cell marker CD133, while Notch blockade reduced 
CD133 expression. We found a strong correlation between CT 
and BLI imaging of tumor growth in vivo (Pearson coefficient 
(r)=0.85, p=0.001). The potential of Notch inhibition 


EP-1350: Malignant mucosal melanoma in the upper aerodigestive tract treated with carbon ion RT at CNAO: preliminary results 

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EP-1350: Malignant mucosal melanoma in the upper aerodigestive tract treated with carbon ion RT at CNAO: preliminary results

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